Abstract

Objectives Postpartum haemorrhage (PPH) is a major cause of maternal mortality and morbidity worldwide. Experimental studies support
the hypothesis that oxytocin administration during labour, a common although not evidence-based practice, may increase the
risk of atonic PPH. The clinical studies, however, are inconclusive. The objectives of this study was to investigate the association
between the level of oxytocin exposure during labour and the risk of severe PPH and to explore whether the prophylactic use
of oxytocin after birth modifies this association.

Design Population-based, cohort-nested case–control study.

Setting 106 French hospitals from December 2004 through November 2006.

Participants Women with term singleton vaginal deliveries, after an uncomplicated pregnancy. Cases were 1483 women with severe PPH, defined
by peripartum change in haemoglobin of ≥4 g/dl or need for blood transfusion. Controls were 1758 women from a random sample
of parturients without PPH.

Main outcome measures The independent association between the level of oxytocin during labour and the risk of severe PPH was tested and quantified
with ORs through two-level multivariable logistic regression modelling.

Results Oxytocin was administered during labour to 73% of cases and 61% of controls (crude OR: 1.7, 95% CI 1.5 to 2.0). After adjustment
for all potential confounders, oxytocin during labour was associated with a significantly higher risk of severe PPH (adjusted
OR: 1.8, 95% CI 1.3 to 2.6) in women who did not receive prophylactic oxytocin after delivery; the OR for haemorrhage increased
from 1 to 5 according to the level of oxytocin exposure. In women who had prophylactic oxytocin after delivery, this association
was significant only for the highest exposure categories.

Conclusions Oxytocin during labour appears to be an independent risk factor for severe PPH. The results emphasise the need for guidelines
clarifying the evidence-based indications for this procedure and the minimal useful regimens.

Funding The Pithagore6 project was funded by the French Ministry of Health under its Clinical Research Hospital Program (contract
number 27-35) and the Caisse Nationale d'Assurance Maladie (CNAMTS). JB was supported by a grant from the Fonds d'Etudes et
de Recherche du Corps Médical of Assistance Publique Hôpitaux de Paris. These funders had no role in the design and conduct
of the study, no role in the collection, analysis or interpretation of the data and no role in the writing of the manuscript
or in the decision to submit for publication.

Contributors JB participated in the design of the study, conducted the analysis, participated in the interpretation of the data and the
drafting and revision of the paper and has seen and approved the final version. He has no conflicts of interest. GK participated
in the design of the study, supervised the analysis and interpretation of the data and participated in the drafting and revision
of the paper. He has seen and approved the final version. He has no conflicts of interest. CD participated in the design of
the study, obtained funding for it, participated in the central monitoring of data collection, the cleaning of the data and
the revision of the paper and has seen and approved the final version. She has no conflicts of interest. R-CR initiated the
collaborative project, obtained funding for it, participated in the design of the study and the revision of the paper and
has seen and approved the final version. He has no conflicts of interest. M-HB-C participated in the design of the study,
obtained funding for it, participated in the revision of the paper and has seen and approved the final version. She has no
conflicts of interest. CD-T participated in the design of the study, obtained funding for it, participated in the central
monitoring of data collection, supervised the cleaning, analysis and interpretation of the data and the drafting and revision
of the paper and has seen and approved the final version. She had full access to all the data in the study and had final responsibility
for the decision to submit for publication. She has no conflicts of interest.